A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD
A caspase-activated DNase that degrades DNA during apoptosis, and its inhibitor ICAD
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DOI：
10.1038/34112
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发表时间：
1998-01-01
期刊：
影响因子：
64.8
通讯作者：
Nagata, S
中科院分区：
文献类型：
--
作者：
Enari, M;Sakahira, H;Nagata, S
动物的体内平衡不仅受细胞的生长和分化的调节，而且还受通过称为凋亡的过程的细胞死亡的调节。细胞凋亡由蛋白酶的半胱天冬酶家族的成员介导，并最终导致染色体DNA的降解。一种半胱天冬酶激活的脱氧核糖核酸酶（CAD）及其抑制剂（ICAD）现已被确定在小鼠淋巴瘤细胞的细胞质部分。CAD是一种由343个氨基酸组成的蛋白质，携带核定位信号; ICAD以长和短形式存在。重组ICAD特异性抑制CAD诱导的DNA降解及其DNA酶活性。当CAD与ICAD在COS细胞或无细胞系统中表达时，CAD作为与ICAD的复合物产生：用半胱天冬酶3处理释放DNA酶活性，其导致细胞核中的DNA片段化。因此，ICAD似乎在其合成期间充当CAD的伴侣，保持与CAD复合以抑制其DNA酶活性;由凋亡刺激激活的半胱天冬酶然后切割ICAD，允许CAD进入细胞核并降解染色体DNA。
The homeostasis of animals is regulated not only by the growth and differentiation of cells, but also by cell death through a process known as apoptosis. Apoptosis is mediated by members of the caspase family of proteases, and eventually causes the degradation of chromosomal DNA. A caspase-activated deoxyribonuclease (CAD) and its inhibitor (ICAD) have now been identified in the cytoplasmic fraction of mouse lymphoma cells. CAD is a protein of 343 amino acids which carries a nuclear-localization signal; ICAD exists in a long and a short form. Recombinant ICAD specifically inhibits CAD-induced degradation of nuclear DMA and its DNase activity. When CAD is expressed with ICAD In COS cells or in a cell-free system, CAD is produced as a complex with ICAD: treatment with caspase 3 releases the DNase activity which causes DNA fragmentation in nuclei. ICAD therefore seems to function as a chaperone for CAD during its synthesis, remaining complexed with CAD to inhibit its DNase activity; caspases activated by apoptotic stimuli then cleave ICAD, allowing CAD to enter the nucleus and degrade chromosomal DNA.